2-oxazolidone compounds and method for preparing the same



and aryl radicals.

Patented Apr. 23, 1946 UNITED STATES PATENT OFF ICE 2-OXAZOLIDONE COMPOUNDS AND METHOD, FOR PREPARING THE SAME August H. Homeyer,

St. Louis, Mo., assignor to Mallinckrodt Chemical Works, St. Louis, Mo., a corporation of Missouri No Drawing. Application February 13, 1942, Serial No. 430,741

21 Claims.

This invention relates to five-membered ring compounds, and more particularly, to z-oxazolidones.

Among the objects of this invention are the preparation of new compounds of the 2-oxazolidone series; the provision of a convenient methodfor making z-oxazolidones; and the provision of an improved method for the economical preparation of compounds of this type. Other objects will be in part obvious and in part pointed out hereinafter.

The invention accordingly comprises the ingredients and combinations of ingredients, the proportions thereof, steps and sequence of steps, and features ofcompcsition and synthesis, analysis, or metathesis, which will be exemplified in the products and processes hereinafter described,

and the scope of the application of which will be indicated in the following claims.

According to the present invention, 2-oxazolidones are prepared by the reaction of a fi-amino alcohol and an alkyl carbonate. The reaction may be rep-resented by the following equation:

alkyl-'0 In the above equation, the Rs are selected from hydrogen, alkyl radicals, hydroxy alkyl radicals different. Alkyl carbonates in general are suitable. Typical carbonates are diethyl carbonate, di-n-propyl carbonate, 'di-n-butyl carbonate and di-secondary butyl carbonate. Unsymmetrical carbonates can be used.

The reactants are heated together, and the alcohol formed is preferably removed by fractionation to force the reaction to completion. In many instances a small amount of a catalyst, consisting of an alkaline metallic compound, is necessary to cause the reaction to take place at ordinarily avail able conditions. Suitable catalysts are, for example, sodium methylate, magnesium methylate, potassium hydroxide and sodium carbonate, al-

though other alkaline metallic compounds may be substituted. Although the function of the catalyst has not been completely determined, it is believed that the active element is in all cases The ES may be the same or a metal alkyl carbonate formed from the catalyst which is actually added.

p-Amino alcohols in general are suitable, even though they contain an additional functional group. These amino alcohols will react with one equivalent of alkyl carbonate to give the 2-oxazolidone. The resulting -2-oxazolidone may, how-' ever, be made to undergo further reaction with the alkyl carbonate where an additional functional group is present, to give more complex products.

The reaction materials must be free of moisture before the reaction will begin. The system may be dried conveniently by distilling offmoist alkyl carbonates, or by adding toluene and distilling off a mixture of toluene and water. Other methods may also be employed to remove moisture from the system.

Wherever the term alkyl appears, it will be understood that cycloalkyl radicals or compounds are included. Likewise where the term alkyl or "ary appears, it will be understood that substituted alkyls or aryls are likewise suitable, as are aralkyls.

The following examples illustrate the invention:

EXAMPLE 1 Ethanolamine A three-necked flask was chanical stirrer and an efiicient fractionating column. Ethanolamine (61 g), diethyl carbonate (150 ml), and sodium methylate (0.5 g.) were placed in the flask. The reaction mixture was stirred and the flask was heated in an oil bath. As the reaction progressed, and was removed as distillate at the head of the column. A total of 112 m1. of alcohol, corresponding to two moles per mole of ethanolamine, was obtained. The residue in the flask solidified on cooling; it was recrystallized from 100 ml. of chloroform. Two crops of 2-oxazolidone were obtained, weighing a total of 57 g.,and representing 65% of the theoretical 'yield. The product melted at 8.7-89 C. 2-Oxazolidone (3 g.) was acetylated by boiling with acetic anhydride (20 ml.) and sodium acetate (1 g.) for 1.5 hours. Excess acetic anhydride was distilled off under reduced pressure and the residue was recrystallized from a mixture of benzene and ether. After sublimationin a high vacuum at 65 C. the pure 3-acety1-2-oxazolidone melted at 69-70 C. It was soluble in water and its solution was neutral to litmus. Analysis of the new compound gave 10.9% nitrogen, compared to the theoretical calculated for CsHIOaN of 10.85%.

Boiling 2-oxazolidone (9 g.) with acetyl chlofitted with a mealcohol was formed 52.1% carbon, 1.8%

CH9O2N of 52.2%, 7.8% and 12.2%

EXAMPLE 2 v Z-amino-Z-methyl-lmmpanlol Z-amino-Z-methyl- -propanol (89. g.) and diethyl carbonate (210 ml.) were placed in the apparatus described in Example 1. The system was dried by distilling ofi moist diethyl carbonate (40 ml.) The flask was cooled and sodium methylate (0.5 g.) was added as a catalyst, and then heating was continued. As the reaction progressed, al-

EXAMPLE 5 Z-omino-S-hexanol 2 amino-3-hexanol (60 g.) and diethyl carbonate (350 ml.) were placed in the apparatus described in Example 1, and the system was dried by distilling until 50 ml. of diethyl carbonate had been collected. Sodium methylate (1 g.) was added as a catalyst and heating was continued until 55 ml. of alcohol had been collected as distillate. The reaction mixture was filtered, excess diethyl carbonate was removed by distillation under reduced pressure, and the residual oil was fractionated through an indented column. 4- methyl-5+propyl-2oxazolidone was an oil which boiled zit-133 C. at 1.5 mm. pressure and its in- :dex of refraction was no 1.4581. The yield was cohol was formed and a total of 115 ml. was obtained as distillate. Excess diethyl carbonate was removed by distillation under reduced pressure. The residue solidified on cooling. The product was purified by recrystallization from a mixture of alcohol and petroleum ether. The yield of 4,4-dimethyl- -oxazo1idone was 83 g. or 72% of the theoretical. The product melted at 5556 C., and was very soluble in water, alcoholor benzene. Analysis of the new compound gave 52.2% carbon, 7.9% hydrogen, and 12.2% nitrogen, compared to the theoretical calculated for C5H9O2N or 52.2%, 7.8% and 12.2% respectively. Determination of the molecular weight gave 112, compared to the theoretical of 115.

Examrrs 3 z-ami-no-z-methyl-z-propanol v EXAMPLE l Z-amino-Z-butanol 2-amino-1-butanol (89 g.) and diethyl carbonate (350 ml.) were placed in the apparatus described in Example 1, and the system was dried by distilling under 200 mm. pressure until 55 ml. of diethyl carbonate had been collected. Sodium methylate (l g.) was added as a catalyst and the reaction mixture was heated at atmospheric pressure. Alcohol was formed as the reaction proceeded,- and a total of 120 ml. was collected as distillate. Excess diethyl carbonate was distilled off under reduced pressure. The residue was crystallized from a mixture of chloroform and petroleum ether by cooling with solid carbon dioxide. The yield of l-ethyl-Z-oxazolidone was 57 g. It melted at 16-165 C. and its index of refraction was no 1.4631. The product was very soluble in water and the solution was neutral to litmus. Analysis of the new compound gave hydrogen and 12.3% nitrogen, compared to the theoretical calculated for respectively.

62g. Analysis of the new compound gave 58.8% carbon, and 9.0% hydrogen, compared to the theoretical calculated for CrI-lmOzN of 58.7% and respectively.

EXAMPLE 6 Diethanolamine Diethanolamine (105 g.), diethyl carbonate (130 -g.), and sodium methylate (0.5 g.) were placed in the apparatus described in Example. 1, and heated at atmospheric pressure; Alcohol was formed as the reaction progressed, va total .of 115ml. being collected in 1.25 hours; this corresponds to two moles of alcohol per mole of diethanolamine. Excess diethyl carbonate was removed by distillation under reduced pressure. The residue of crude 3-(2-hydroxyethyl) -2- oxazolidone was a viscous liquid which was soluble in water and insoluble in ether. A sample was purified by molecular distillation in a high vac- 175 C. Analysis of the new compound gave 46.0% carbon, and 6.7% hydrogen, compared to the theoretical calculated for CsHsOsN of 45.8% and 6.9% respectively.

A sample of the product (3.5 g.) was dissolved in a little chloroform and phenylisocyanate (2.8 g.) dissolved in ether was added. The solvents were boiled off and the residue was recrystallized from benzene. The phcnyl urethane of 3-(2- hydroxyethyl)- -oxazolidone melted at 101-102 -C. Analysis of the new compound gave 11.2% nitrogen, compared to the theoretical calculated for C12H14O2N2 of 11.2%.

3-(2-hydroxyethyl) -2-oxazo1idone (2.5 g.) and benzoyl chloride (2.5 ml.) were heated at C. until hydrogen chloride was no longer evolved. The product was crystallized from methyl alcohol by cooling in solid carbon dioxide and then from a mixture of methyl alcohol and ether. It was sublimed in a high vacuum at C. The benzoate of 3-(2-hydroxyethyl) -2-oxazolidone melted at 69-70". C. Analysis of the new compound gave 5.95% nitrogen, compared t the theoretical calculated for CiaHisOlN of 5.95%.

Exempt: 'Z

uum at about Z-amino-l-phenyZ-1 ;oropanolresidue: was a viscous crystallize.

tion mixture was heated distillate.

cooling. It was tral to litmus. gave. 46.0% nitrogen, compared to the theoretical calculated fagaaaizrs in: chloroform. and." mixed with. petroleum ether.

The solid which separated weighed 21 g. After removingthe solvent from the mother liquor, the oil which weighed 37 g. The solid and. the oil thus obtained represent diastereomeric mixtures of 4-methyl-5-phenyL-2- oxazolidone. The solid product was recrystallized from. a mixture of chloroform and petroleum ether and then from benzene. After sublimation in a high vacuum at 130 0., the product melted at 96-93 C. Analysis of'the new product gave 67.9% carbon, 6.0% hydrogen, and 8.0% nitrogen,

compared to the theoretical calculated .for"

CmHuOzN of 67.8%, 6.3% and 7.9% respectively.

The solid, melting at 96-98" 0., was dissolved in about parts of warm benzene and allowed to The solid which separated was recrystallized, and then sublimed in a high vacuum. The product, a mixture of the 2-oxazolidones derived from the isomers of Z-amino-l-phenyl-lpropanol, melted at 145-147 C. Analysis of the new product gave 7.96% nitrogen, compared to the theoretical calculated for C10H11O2N of 7.90%.

EXAMPLE 8 Ephedrine Ephedrine alkaloid (16.5 g.) and dipropyl carbonate (40 g.) were placed in the apparatus described in Example 1, and the system was dried by distilling at a pressure of 100 mm. until ml. of dipropyl carbonate had been collected. Sodium methylate (0.2 g.) was added and the reacat atmospheric pressure in an-oil bath-at 160 C. The temperature of the reaction mixture was about 131 0., and 14 ml. of propyl alcohol, B. P. 95" 0., were collected as Then the pressure was reduced to 100 mm. and excess dipropyl carbonate was distilled on. The residue was a liquid which solidified on recrystallized .from benzene and washed with ether. The yield of 3,4-dimethyl- 5-phenyl-2-6xaz0lidone was 17 g. or 89%. of the theoretical.

' The product melted at 90-92 C.,, sublimed in a high vacuum at 90 C., was soluble in chloroform or benzene, and less soluble in water or ether. The solution in water was neutral to litmus.

,Analysis gave 7.3% nitrogen, compared to. the

theoretical calculated for C11H13O2N of 7.3%. The compound was levo rotatory, [(11 being up to ml. of solution with 95% alcohol.

EXAMPLE 9 2-amz'no-2-methyl-1,3-pr0panediol 2-amino 2 methyl-1,3-propanediol (52.5 g.) and diethyl carbonate (59 g.) were placed in the apparatus described in Example land heated by an oil bath. Alcohol began to be collected at the head of the column when the temperature of the reaction. mixture was 120 C. A total of 44 g. of alcohol was collected as distillate in two hours. At the end of the heating period, the temperature of the reaction mixture was 179 solidified on cooling. It weighed 65 g. Recrystallization from anhydrous alcohol (75 ml.) gave a first crop weighing 50 g., and 'asecond crop .weighing 14 g. The pure 4-methyl-4-hydroxymethyl-2-oxazolidone melted at 115-116.5 C. The product sublimed in a high vacuum at 135 C. It-.-was soluble in water and the solution was neu Analysis of the new compound carbon, 6.7% hydrogen, and 10.7%

C. The product Y 95 when 0.6563 g. of the substance was made Monoethyl ethanolamine (45 g.) and diethyl carbonate (350 mil were placed in the apparatus described in Example 1 and the system was dried by distilling at 200 mm. pressure until 50 ml. of diethyl carbonate had been collected. Sodium methylate (1 g.) was added, and-he'atingwascontinued at atmospheric pressure until 58' ml. of alcohol had' been-obtained as distillate. Fractionation gave two" products: 3-ethyl-2-oxazolidone (42 g.), B. P. 92 C. at 1 mm., n 1.4490; and an oil, B. P. C. at 1 mm., 11. 1.4308. The 3- ethyl-2-oxazolidone was soluble in water, giving a solution which was neutral to litmus; the pure compound appeared to be hydroscopic. Analysis of the new compound gave.11.4% nitrogen, compared to the theoretical calculated for CeHOzN of 12.1%.

V The oil; B. P. 105 C. at 1mm was-the ethyl carbonic ester of N-ethyl-N-(p-hydroxyethyl) urethane:

EXAMPLE 11 Monoethyl ethanolamine Monoethyl ethanolamine (45 g.) and dibutyl carbonate (134 g.) were placed in the apparatus described in'Example 1, and the system was dried by distilling at 42 mm. pressure u'ntil32 g. dibutyl carbonate had been collected as distillate. Magnesium methylate (0.5 g.) dissolved in methanol (15 ml.) was added, and the reaction mixture was heated to about C. at atmospheric pressure. and butyl alcohol (40 ml.) ,were obtained as distillate in one hour. Fractionation of the product gave 3-ethyl-2-oxazolidone, B. P. 78 C. at 0.5 mm., n 1.4490. Theproduct was identical withthe 3-ethyl-2- oxazolidone obtained in Example 10. e

I EXAMPLE 12 Mono ngbutyl I ethanolamine placed in the apparatus described in Example :1. off todry the system.

alyst, and heating was continued at 690' mm. pressure, 70 ml. of butyl alcohol being obtained as distillate in 0.5 hour. The reaction mixture was filtered to remove the little solid matter present. Fractionation gave 3-n-butyl-2-oxazolidone, B. P. 94 C. at 1 mm., n' -5 1.4515. The yield was 83%. Analysis'ofzthe new compound :gave..9.-5% nitrogen; comparedrto the theoretical calculated for C7H13O2N of.'9'.8%,.

nitrogen, compared EXAMPLE 13 Phenyl ethcnolamine Phenyl ethanolamine (68.5 g.) dibutyl carbonate (102 g.) and toluene (40 ml.) were placed in the apparatus described in Example 1, and the toluene was distilled ed to dry the system. Anhydrous sodium carbonate (1 g.) was added, and heating was continued at about 170 C. at atmospheric pressure. Butyl alcohol was formed rapidly, 90 ml. being collected as distillate in 0.5 hour. After cooling, the reaction product was dissolved in hot chloroform (150 ml.), treated with decolorizing carbon, and allowed to crystallize. The product was washed with petroleum ether. A total of 81 g. of 3-phenyl-2-oxazolidone,

M. P. i2o-122.5 0., was obtained. Analysis of the product gave 8.3% ntrogen, compared to the theoretical calculated for CcHcOaN of 8.6%.

EXAMPLE 14 Tris- (hydrorymethyl) -aminomethane Tris-(hydroxymethyl) -aminomethane (60.5 g.) dipropyl carbonate (76 g.) and toluene (100 ml.) were placed in the apparatus described in Example 1. The system was dried by distilling until 15 ml. of toluene had been collected. After addition of sodium methylate (0.5 g.) propyl alcohol was formed, and a mixture of it with toluene was taken off as distillate. The residue remaining in the reaction flask was a syrupy liquid which was dissolved in hot water; the solution was filtered and purified by recrystallization from 95% alcohol. The benzoyl derivative melted at 175.5-176 EXAMPLE 15 Diethzmolamine Diethanolamine (105 g.), diethyl carbonate (300 ml.), and sodium methylate (0.5 g.) were placed in the apparatus described in Example 1. The reaction mixture was heated at atmospheric pressure until 96.5 g. of alcohol, B. P. 78-79" C., had been collected as distillate. Then fractionation was continued at 150 mm. pressure and 35.5 g. more alcoholic distillate was collected at 50 C. at the head of thecolumn. The total alcohol obtained was 132 g. corresponding to 2.87 moles per mole of diethanolamine. Excess diethyl carbonate was removed from the reaction mixture by distillation under reduced pressure. The residue was a viscous oil weighing 180 g. This was mixed with 50 ml. anhydrous alcohol and allowed to crystallize, yielding 46 g. of a solid product. The mother liquor was stripped of alcohol, and the residue was mixed with 100 ml. methyl alcohol and cooled in solid carbon dioxide. A second crop of solid product weighing 28 g. was obtained. making a total of 74 g. The remainder of the material failed to crystallize.

The solid product was purified by recrystallization fromalcohol. It melted at 106-108? 0.; could not be sublimed, and was soluble in water, glacial acetic acid, hot alcohol, or hot chloroform. It was sparingly soluble in benzene, ether or diethyl carbonate.

From the method f synthesis, properties, and analysis of the new compound it was bis ['2-(2-oxo- 3-oxazolidyl) ethyl] iminodiethylene carbonate having the structure shown below. I 0 (-O-CHaGHa-AI-CH:OH2-Oy)OCHzCHz-N- CH 4-methyl-4-hydroxymethyl-2-oxazolidone duewas an oil which ylate (1 g.) was Analysis gave 45.85% carbon, 5.38% hydrogen, and 9.96% nitrogen, compared to the theoretical calculated for C16H250ioN3 Of 45.82%, 6.01%, and 10.01% respectively. The molecular weight found was 416 compared to the theoretical of 419.

EXAMPLE 16 Z-amz'no-Z-methyZ-1,3-propanediol 2-amino-2-methyl-1,3-propanediol (52.5 g.) and diethyl carbonate (600 ml.) were placed in the apparatus described in Example 1. 'The' reaction mixture was heated at atmospheric pressure by an oil bath atv 150 C. The temperature of the liquid in the flask was 130 C. and 45 ml. of diethyl carbonate, B. P. 123 C., were collected as distillate during 30 minutes. No alcohol was formed. After cooling somewhat, sodium methadded as a catalyst. Then heating was resumed and alcohol was fractionated out of the reaction mixture at reduced pressure. Ml. of alcohol were collected at 48-50" C. under 200 mm. pressure during 1.? hours. This alcohol corresponded to 3 moles per mole of 2-amino-2- methyl-1,3-propanediol used as starting material. The reaction mixture was filtered t o remov'the trace of solid which had formed, and the excess diethyl carbonate was removed by distillation under reduced pressure. The residue was an oil which weighed g. It was soluble in water, benzene, acetic acid, or ethyl acetate, but was insoluble in ether. It failed to crystallize and attempts to distill it resulted in decomposition. .Analysis of the new product gave 47.0% carbon, 6.5% hydrogen and 7.8% nitrogen. Material similar to the product described above was produced also by the further reaction of with diethyl carbonate in the presence of a trace of sodium methylate. 4-methyl-4-hydroxymethyl- 2-oxazolidone (26 g.) from Example 9 and diethyl carbonate (300 ml.) were placed in the apparatus described in Example 1. The reaction mixture was heated at atmospheric pressure and 30 ml. of diethyl carbonate were collected as distillate. No alcohol was formed. Sodium methylate (0.5 g.) was added as a catalyst, and then 17 ml.'of alcoholic distillate B. P. IQ-81 C., were collected. Then the temperature at the head of the column rose rapidly to the boiling point of diethyl carbonate. The amount of alcohol corresponds to one mole per mole of the oxazolidone used as starting material. The reaction mixture-was filtered to remove the trace of solid which had formed and excess diethyl carbonate was removed by distillation under'reduced pressure. The resiweighed 42 g. The material appeared to be entirely similar'to the'product described in the first paragraph of this example.

the apparatus described in Example-1 and heated under 200 mm. pressure until 50 ml. of diethyl carbonate had been distilled off to dry the system.

Sodium methylate (1 g.) was added as a catalyst and the mixture was heated at 110-126 C. at atmospheric pressure while 120 ml. of alcohol were collected as distillate. The alcohol obtained corresponded tofour moles per mole of the tris-(hydroxymethyl) -aminomethane. A yellowish, taffylike material separated from the diethyl carbonate and was removed by filtration; it weighed 69 g. After removal of excess diethyl carbonate from the mother liquor by distillation an oil remained as a residue. The products failed to crystallize and decomposed when sublimation was attempted. They were polymeric substances.

EXAMPLE 18 2-amino-2-methyZ-1-propanol -2-amino-2-methyl-l-propanol (89 g.), di-sec.- butyl carbonate (191 g.), xylene (100 ml.), and

benzene (50 ml.) were combined in the apparatus described in Example 1 and 40 ml. of benzene were distilled off to dry the system. A suspension of potassium sea-butyl carbonate (0.5 g.) in 25 ml. of sec.-butyl alcohol was added as a catalyst.

The salt was prepared by dissolving potassium a metal in sec.-butyl alcohol and saturating the d-Ephedrine d-Ephedrine (8.25 g.) and Xylene (110 ml.) were placed in the apparatus described in Example 1. The system was dried by distilling ofi 20 ml. of xylene under 150 mm. pressure. Di-npropyl carbonate (14.6 g.) was added, sodium methylate (0.2 g.) was added as a catalyst, and the reaction mixture was heated for two hours. Propyl alcohol ('7 ml.) was collected as distillate. The solution remaining in the flask was treated with decolorizing carbon and then the solvent was removed by distillation under reduced pressure. The residue weighing 9.8 g. solidified on cooling. It was washed with petroleum ether and recrystallized from benzene and petroleum ether. The purified 3,4-dimethyl 5 phenyl 2 oxazolidone Weighed 6.7 g. and melted at 9292.5 C. The compound was dextro rotatory [ch being +945 when "0.5385 g. of the substance was made up to 25 ml. of solution with 95% alcohol.

ExAMPLE dl-Norephedrine dl-Norephedrine (10 g.), diethyl carbonate g.), xylene (100 ml.) and benzene (25 ml.) were combined in the apparatus described in Example 1, and the system was dried by distilling until the benzene had been removed. After cooling somewhat, sodium methylate (0.3 g.) was added as a catalyst and heating was continued. at atmospheric pressure for two hours. About 15' ml, of distillate were collected'which contains about 5.7 ml. of alcohol. .The reaction mixture was distilled to drynessunder 50 mm. pressure. The residue crystallized on cooling. It was dissolved in hot benzene and filtered to remove inorganic impurities. The filtrate was evaporated to a small volume and mixedwith petroleum ether. The 4-methyl-5-phenyl 2 oxazolidone which crystallizedlweighed 9.7 g. and melted at 145'146 C. Amixture of ing diastereomeric isomer, described in Example 7, melted at 145-146 C.

EXAMPLE 21 Z-amz'no-I-phenyl-1-propanol 2-amino- -phenyl-l-propanol g.) and xylene ml.)xwere combined in the apparatus described in Example 1, and the system was dried by distilling under mm. pressure until 30 ml. of xylene had been collected. Diethyl carbonate (91.5 g.) and sodium methylate (0.5 g.) were, added and heatingwas then continued at atmospheric pressure, 78 ml. of alcohol being collected during two hours. The hot solution remaining in the reaction flask was filtered and allowed to crystallize. The solid product which separated melted at 93-100 C. and weighed'86.5 g. The mother liquor was freed of solvent by distillation and there remained 31.1 g. of a liquid residue. These products represent mixtures of the diastereomers of 4-methyl-5-phenyl-2 oxazolidone. By fractional crystallization of the solid product from benzene and absolute alcohol, there was obtained 4-methyl- 5-phenyl-2-oxazolidone, M. P. 146-147 C., which was identical with that prepared irom dl-norephedrine, as described in Example 20.. There. was also obtained from the mother liquors another diastereomer, M. P. 96-96.5 C., which isderived from dl-isonorephedrine.

The 2-oxazolidones are neutral substances soluble in water and organicv solvents. They do not appear. to form salts with acids or bases, nor do they appear to react with bromine. In general, their solubility in water decreases as the length of the carbon chain substituentsincreases. They are physiologically active.

Attention is directed to my oopending applications, Serial No. 648,206 filed February 16, 1946, Serial No. 648,207 filed February 16, 1946, and Serial No. 648,208 filed February 16, 1946.

In view of the above, it will be seen that the several objects of the invention areachieved' and other advantageous results attained.

As many changes could be made in the above methods and products without departing from the scope of the invention, it is intended that all matter contained in the above description shall be interpreted as illustrative and not in a limiting sense.

I claim:

1. 3- (2-hydroxyethyl) -2-oxazolidone.

2. 3,4-dimethyl-5-pheny1-2-oxazolidone.

3. 4,4-di- (hydroxymethyl) -2-oxazolidone.

4. Dextro rotary 3,4-dimethyl-5-phenyl-2-oxazolidon, r I v r 5. Levo rotary '3,4-dimethyl-5-phenyl-2 oxazolidone. A

6. The method of making 2-oxazolidones which I comprises mixing a ,B-amino alcohol, a dialkyl carbonate and an alkaline metallic compound eatthis product with the high meltalyst under substantially anhydrous conditions, and condensing the moisture-free mixture to directly form a 2-oxazolidone.

7. The method of making 2-oxazolidone which comprises mixing a ii-amino. alcohol, a dialkyl carbonate and an alkaline metallic compound cat comprises mixing a p-amino alcohol with a dialkyl carbonate, said mixture inherently containing moisture, heating the mixture to remove substantially all of said moisture, permitting the mixture to cool below the temperature of moisture removal, adding an alkaline metallic compound catalyst to the moisture-free mixture, and heating the resultant mixture to directly form a 2- oxazolidone.

10. The method of making 2-oxazolidones which comprises mixing a fl-amino alcohol with a dialkyl carbonate, said mixture inherently containing moisture, heating the mixture under reduced pressure to remove substantially all of said moisture,permitting the mixture to cool below the temperature of moisture removal, adding an alkaline metallic compound catalyst to the moisture-free mixture, and heating the resultant mixture at atmospheric pressure to directly form a 2-oxazolidone.

11. The method of making 2-oxazolidones which comprises mixing a p-amino alcohol with a dialkyl carbonate, said mixture inherently containing moisture, heating the mixture to distill ofi a minor proportion of the dialkyl carbonate with substantially all the moisture, permitting the mixture to cool, adding as a catalyst an alkali metal alcoholate, and condensing the resultant mixture to directly form a 2-oxazolidone.

12. The method of making z-oxazolidones which comprises mixing a p-amino alcohol with a dialkyl carbonate, said mixture inherently containing moisture, heating the mixture to distill oil moist dialkyl carbonate under reduced pressure conditions, adding as a catalyst an alkaline earth metal alcoholate, and'subjecting the resultant mixture to distillation for directly condensing the alcohol and carbonate to form a 2-oxazolidone and for continuously removing alcohol formed in the reaction.

13. The method of making 3,4-dimethyl-5- phenyl-Z-oxazolidone which comprises preparing an anhydrous mixture of ephedrine alkaloid and a dialkyl carbonate, said reagents inherently containing moisture, adding to the resultant mixture an alkali metal alcoholate as a catalyst and heating the resultant mixture to directly form the 2- oxazolidone and to distill ofi alcohol formed by the reaction.

14. The method of making 3,4-dimethyl-5- phenyl-Z-oxazolidone which comprises preparing an anhydrous mixture of ephedrine alkaloid and dipropyl carbonate, said reagents inherently containing moisture, addingto the resultant-mixture an alkali metal, alcoholate as a catalyst and heating the resultant mixture to directly form the 2-oxazolidone and to distill off alcohol formed by the reaction.

15. The method of making 3,4-dimethyl-5- phenyl-2-oxazolidone which comprises mixing ephedrine alkaloid with a dialkyl carbonate, said mixture inherently containing moisture, distil ling the mixture under reduced pressure until a minor proportion of the dialkyl carbonate is removed with substantially all the moisture con tent of the mixture, adding as a catalyst for the resultant mixture an alkali metal alcoholate, and heating the resultant mixtureunder atmospheric pressure to directly form the 2-oxazolidone and to distill off alcohol formed by the reaction,-

16. The method of making 3-(2-hydroxy ethyl) -2-oxazolidone which comprisespreparing an anhydrous mixture of diethanolamine and .a dialkyl carbonate, 'said reagentsinherently containing moisture, adding to the resultant mix ture an alkali metal alcoholate as a catalyst, and heating the resultant mixture to directly form the 2-oxazolidone and to distill off alcohol formed by the reaction.

17. The method of making 3-(2-hydroxyethyl) -2-oxazolidone which comprises preparing an anhydrous mixture of diethanolamine and diethyl carbonate, said reagents inherently containing moisture, adding to the resultant mixture an alkali metal alcoholate as a catalyst, and heating the resultant mixture to directly form the 2-oxazolidone and to distill ofi alcohol formed by the reaction. 1

18. The method of making a 2-oxazolidon'e which comprises preparing an anhydrous mix ture of diethanolamine and a dialkyl carbonate containing an alkali metal alcoholate as a cata lyst,-heating the resultant mixture under atmospheric pressure to distill off a portion of the alcohol formed by the reaction, continuing the heating under reduced pressure to remove the remainder of the and to remove excess carbonate, the '2-oxazolidone being directly iormed during said heat treatment.

19. The method of making a 2 -oxazolidone which comprises preparing an anhydrous mixture of tris (hydroxymethyl)-aminomethane and a dialkyl carbonate, said reagents inherently containing moisture, adding to the resultant mix: ture an alkali metal alcoholate as a catalyst, and heating the resultant mixture to directly form the 2-oxazolidone and to remove alcohol formed by the reaction.

20. The method of making 4,4-di-(hydroxymethyl) -2-oxazolidone which comprises mixing tris- (hydroxymethyl) -aminomethane with a di alkyl carbonate and toluene, said mixture inherently containing moisture, distilling off a minor portion of the toluene with the moisture content to dry the mixture, adding an alkali metal alcoholate as a catalyst to the resultant mixture, and heating the latter mixture to dis: till ofi'the remainder of the toluene and alcohol formed by the reaction and to directly form the 2-oxazolidone;

21. A 2-oxazolidone selected, from the group consisting of 3-(2-hydroxyethyl) -2-oxazolidone, 3,4-dimethyl-5-phenyl-2-oxazolidone and 4,4- di-(hydroxymethyl) -2-0xazolidone. AUGUST H. HOMEYER.-

alcohol formed by the reaction- 

